Tiopronin

Tiopronin is a diffusible antioxidant, an antidote to heavy metal poisoning and a radioprotective agent. Tiopronin can control the rate of cystine precipitation and excretion and has the potential for cystinuria, rheumatoid arthritis and hepatic disorders^[1][2]. In Vitro: In in vitro Von Hippel-Lindau protein binding assay, the inhibitory effect of Tiopronin (NMPG) on HPH-2 was attenuated by escalating dose of ascorbate but not 2-ketoglutarate, cofactors of the enzyme^[2]. In Vivo: Tiopronin (NMPG) alleviates colonic injury and effectively lowered myeloperoxidase activity. Moreover, NMPG substantially attenuates expression of pro-inflammatory mediators in the inflamed colon. NMPG induces hypoxia-inducible factor-1α (HIF-1α) in human colon carcinoma cells, leading to elevated secretion of vascular endothelial growth factor (VEGF), a target gene product of HIF-1 involved in ulcer healing of gastrointestinal mucosa. NMPG induces HIF-1α occurred by inhibiting HIF prolyl hydroxylase-2 (HPH-2), an enzyme that plays a major role in negatively regulating HIF-1α protein stability^[2].